Some types of hypertension in man are associated with an increase in total peripheral resistance, a negative potassium balance, hypokalemia and lowered total body potassium (primary aldosteronism, for example). We hypothesize that the increase in total peripheral resistance and hence the hypertension are causally related to altered potassium concentrations in the blood vessel wall. Specifically, we suspect that the intracellular concentration of potassium in the smooth muscle is reduced more in absolute terms than the extracellular concentration, resulting in a decreased potassium gradient, decreased membrane potential and contraction. Our aim is to test this hypothesis by producing changes in the potassium gradient in various intact vascular beds and correlating these changes with any alterations in the resistance to blood flow. Miniature dializers will be interposed in the arterial supply of the gracilis muscle, foreleg, kidney and heart, and perfusion pressure measured at constant flow. Potassium (and later magnesium) will be removed from the perfusing blood for both brief (5 min.) and prolonged periods (one to two hours). Utilizing plasma and tissue analysis for potassium and measurements of inulin space, changes in the potassium gradient will be calculated and correlated with the changes in resistance. These studies are important because they are directed at the mechanism of hypertension at the blood vessel level.